Numerous protein growth factors have been isolated and characterized in recent years. These growth factors include epidermal growth factor, fibroblast growth factors, insulin-like growth factors, transforming growth factors, platelet-derived growth factor and interleukins. For example, fibroblast growth factor ("FGF") was first purified by Gospodarowicz in 1975 from bovine pituitary and had an estimated molecular weight of 13,300 daltons (Reference 1).
FGF was later purified from bovine brain (2). FGF can be isolated in either an acidic ("aFGF") or basic ("bFGF") form, depending on the isolation procedures used (3,4). A complete amino acid sequence for bovine pituitary bFGF (5) and bovine and human brain aFGF (6,7) has been published, together with the N-terminal sequences for bovine and human brain bFGF (5). The N-terminal sequences for bovine pituitary and bovine brain bFGF are identical (5,8).
It has now been found that, when the FGFs are purified from brain tissue using heparin-Sepharose affinity chromatography (9,10), a significant quantity of unknown proteins may also be present. Because proteins that bind with particularly high affinity to heparin are rare, further study of these unknown proteins was undertaken. This investigation revealed these proteins to be the HBBMs, which differ from the FGFs in their N-terminal sequence and amino acid compositions.
Accordingly, it is an object of this invention to isolate, purify and characterize the HBBMs from brain tissue. It is a further object of this invention to establish the physiological activity of the HBBMs.